Publications by authors named "Kathleen E Malone"

174 Publications

Mammographic texture features associated with contralateral breast cancer in the WECARE Study.

NPJ Breast Cancer 2021 Nov 29;7(1):146. Epub 2021 Nov 29.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

To evaluate whether mammographic texture features were associated with second primary contralateral breast cancer (CBC) risk, we created a "texture risk score" using pre-treatment mammograms in a case-control study of 212 women with CBC and 223 controls with unilateral breast cancer. The texture risk score was associated with CBC (odds per adjusted standard deviation = 1.25, 95% CI 1.01-1.56) after adjustment for mammographic percent density and confounders. These results support the potential of texture features for CBC risk assessment of breast cancer survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-021-00354-1DOI Listing
November 2021

Racial/ethnic disparities in risk of breast cancer mortality by molecular subtype and stage at diagnosis.

Breast Cancer Res Treat 2021 Dec 15;190(3):549-558. Epub 2021 Oct 15.

University of Washington, Seattle, WA, USA.

Purpose: Previous research has found significant survival disparities between Black and White women among select stages and subtypes of breast cancer, however other racial/ethnic groups have been less well-studied. This study expands on previous research, examining differences in breast cancer-specific mortality across multiple racial and ethnic groups.

Methods: Women diagnosed with a first primary invasive breast cancer between 2010 and 2016 who were 20-85 years of age at diagnosis were identified from 18 Surveillance, Epidemiology, and End Results (SEER) registries. Subtypes were defined by joint hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Cox proportional hazards models for each stage and subtype were fit, with non-Hispanic white women as the reference group. Effect modification by age at diagnosis (< 50, ≥ 50) was found and thus analyses were age-stratified.

Results: After multivariable adjustment, younger Black women had greater risks of breast cancer-specific death for all stages of HR+/HER2-, and certain stages of HR+/HER2+ , TN, and HR-/HER2 + breast cancer. Asian/Pacific Islander women generally had a lower hazard of breast cancer-specific death. Older Hispanic White women had a lower hazard of breast cancer-specific death for stages I-III HR + /HER2- and stage II TN breast cancer.

Conclusions: These findings demonstrate that different racial/ethnic groups experience different risks of breast cancer-specific mortality by stage and subtype. Efforts to address survival disparities should place additional focus on young Black women, as they experience meaningful disparities in breast cancer-specific mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-021-06311-7DOI Listing
December 2021

Receipt of Screening Mammography by Insured Women Diagnosed With Breast Cancer and Impact on Outcomes.

J Natl Compr Canc Netw 2021 07 30. Epub 2021 Jul 30.

Department of Radiology, University of Washington School of Medicine; and.

Background: The purpose of this study was to determine factors associated with receipt of screening mammography by insured women before breast cancer diagnosis, and subsequent outcomes.

Patients And Methods: Using claims data from commercial and federal payers linked to a regional SEER registry, we identified women diagnosed with breast cancer from 2007 to 2017 and determined receipt of screening mammography within 1 year before diagnosis. We obtained patient and tumor characteristics from the SEER registry and assigned each woman a socioeconomic deprivation score based on residential address. Multivariable logistic regression models were used to evaluate associations of patient and tumor characteristics with late-stage disease and nonreceipt of mammography. We used multivariable Cox proportional hazards models to identify predictors of subsequent mortality.

Results: Among 7,047 women, 69% (n=4,853) received screening mammography before breast cancer diagnosis. Compared with women who received mammography, those with no mammography had a higher proportion of late-stage disease (34% vs 10%) and higher 5-year mortality (18% vs 6%). In multivariable modeling, late-stage disease was most associated with nonreceipt of mammography (odds ratio [OR], 4.35; 95% CI, 3.80-4.98). The Cox model indicated that nonreceipt of mammography predicted increased risk of mortality (hazard ratio [HR], 2.00; 95% CI, 1.64-2.43), independent of late-stage disease at diagnosis (HR, 5.00; 95% CI, 4.10-6.10), Charlson comorbidity index score ≥1 (HR, 2.75; 95% CI, 2.26-3.34), and negative estrogen receptor/progesterone receptor status (HR, 2.09; 95% CI, 1.67-2.61). Nonreceipt of mammography was associated with younger age (40-49 vs 50-59 years; OR, 1.69; 95% CI, 1.45-1.96) and increased socioeconomic deprivation (OR, 1.05 per decile increase; 95% CI, 1.03-1.07).

Conclusions: In a cohort of insured women diagnosed with breast cancer, nonreceipt of screening mammography was significantly associated with late-stage disease and mortality, suggesting that interventions to further increase uptake of screening mammography may improve breast cancer outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6004/jnccn.2020.7801DOI Listing
July 2021

Smoking, Radiation Therapy, and Contralateral Breast Cancer Risk in Young Women.

J Natl Cancer Inst 2021 Mar 29. Epub 2021 Mar 29.

Memorial Sloan Kettering Cancer Center, New York, NY.

Evidence is mounting that cigarette smoking contributes to second primary contralateral breast cancer (CBC) risk. Whether radiation therapy (RT) interacts with smoking to modify this risk is unknown. In this multicenter, individually-matched case-control study, we examined the association between RT, smoking, and CBC risk. The study included 1,521 CBC cases and 2,212 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985-2008 at age <55 years. Absorbed radiation doses to contralateral breast regions were estimated with thermoluminescent dosimeters in tissue-equivalent anthropomorphic phantoms and smoking history was collected by interview. Rate ratios (RRs) and 95% confidence intervals (CIs) for CBC risk were estimated by multivariable conditional logistic regression. There was no interaction between any measure of smoking with RT to increase CBC risk (eg, the interaction of continuous RT dose with smoking at first breast cancer diagnosis [ever/never]: RR = 1.00, 95% CI = 0.89-1.14; continuous RT dose with years smoked: RR = 1.00, 95% CI = 0.99-1.01; and continuous RT dose with lifetime pack-years: RR = 1.00, 95% CI = 0.99-1.01). There was no evidence that RT further increased CBC risk in young women with first primary breast cancer who were current smokers or had smoking history.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djab047DOI Listing
March 2021

Bisphosphonate Use and Breast Cancer Risk among Women with Ductal Carcinoma .

Cancer Res 2021 05 24;81(10):2799-2802. Epub 2021 Mar 24.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Women with a history of ductal carcinoma (DCIS) have an elevated risk of a subsequent invasive breast cancer, but there are few established potentially modifiable factors known to lower this risk. Bisphosphonates are a commonly used treatment for patients with osteoporosis and have been shown to lower risks of recurrence and mortality in patients with invasive breast cancer; however, their use has not previously been investigated within the context of DCIS. Utilizing a population-based nested case-control design, we compared 301 cases of women diagnosed with DCIS and a subsequent breast cancer and 587 individually matched controls (on age, DCIS diagnosis year, primary treatment, histology, grade, and disease-free survival time) who were diagnosed with DCIS but never a subsequent breast cancer. Information on recency and duration of bisphosphonate use was ascertained from patient interviews and medical record reviews. Current users of bisphosphonates had a reduced risk of developing an invasive breast cancer compared with never users [OR = 0.50; 95% confidence interval (CI): 0.26-0.99]. Users of bisphosphonates for ≥48 months had a similar reduction in risk (OR = 0.45; 95% CI, 0.24-1.06). This is the first study to document that bisphosphonate use is associated with a lower risk of subsequent invasive breast cancer among women with a history of DCIS. This finding is consistent with the protective effect of bisphosphonates observed in other breast cancer settings. If validated by others, bisphosphonates may be an effective risk-reducing approach with the potential added benefits of its positive impacts on bone health and fracture risk. SIGNIFICANCE: This study finds that bisphosphonate use among women with a history of DCIS is associated with lower risk of subsequent invasive breast cancer, providing a potential preventative approach for this high-risk population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-20-4100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285031PMC
May 2021

Race, ethnicity and risk of second primary contralateral breast cancer in the United States.

Int J Cancer 2021 06 24;148(11):2748-2758. Epub 2021 Feb 24.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33501DOI Listing
June 2021

A case-control study of the joint effect of reproductive factors and radiation treatment for first breast cancer and risk of contralateral breast cancer in the WECARE study.

Breast 2020 Dec 24;54:62-69. Epub 2020 Aug 24.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Objective: To examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC).

Methods: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity).

Results: Nulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast.

Conclusion: Among young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman's risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.breast.2020.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494790PMC
December 2020

Radiation Treatment, ATM, BRCA1/2, and CHEK2*1100delC Pathogenic Variants and Risk of Contralateral Breast Cancer.

J Natl Cancer Inst 2020 12;112(12):1275-1279

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Whether radiation therapy (RT) affects contralateral breast cancer (CBC) risk in women with pathogenic germline variants in moderate- to high-penetrance breast cancer-associated genes is unknown. In a population-based case-control study, we examined the association between RT; variants in ATM, BRCA1/2, or CHEK2*1100delC; and CBC risk. We analyzed 708 cases of women with CBC and 1399 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2000 and aged younger than 55 years at diagnosis and screened for variants in breast cancer-associated genes. Rate ratios (RR) and 95% confidence intervals (CIs) were estimated using multivariable conditional logistic regression. RT did not modify the association between known pathogenic variants and CBC risk (eg, BRCA1/2 pathogenic variant carriers without RT: RR = 3.52, 95% CI = 1.76 to 7.01; BRCA1/2 pathogenic variant carriers with RT: RR = 4.46, 95% CI = 2.96 to 6.71), suggesting that modifying RT plans for young women with breast cancer is unwarranted. Rare ATM missense variants, not currently identified as pathogenic, were associated with increased risk of RT-associated CBC (carriers of ATM rare missense variants of uncertain significance without RT: RR = 0.38, 95% CI = 0.09 to 1.55; carriers of ATM rare missense variants of uncertain significance with RT: RR = 2.98, 95% CI = 1.31 to 6.80). Further mechanistic studies will aid clinical decision-making related to RT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djaa031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735763PMC
December 2020

Association of a Pathway-Specific Genetic Risk Score With Risk of Radiation-Associated Contralateral Breast Cancer.

JAMA Netw Open 2019 09 4;2(9):e1912259. Epub 2019 Sep 4.

Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: Radiation therapy for breast cancer is associated with increased risk of a second primary contralateral breast cancer, but the genetic factors modifying this association are not well understood.

Objective: To determine whether a genetic risk score comprising single nucleotide polymorphisms in the nonhomologous end-joining DNA repair pathway is associated with radiation-associated contralateral breast cancer.

Design, Setting, And Participants: This case-control study included a case group of women with contralateral breast cancer that was diagnosed at least 1 year after a first primary breast cancer who were individually matched to a control group of women with unilateral breast cancer. Inclusion criteria were receiving a first invasive breast cancer diagnosis prior to age 55 years between 1985 and 2008. Women were recruited through 8 population-based cancer registries in the United States, Canada, and Denmark as part of the Women's Environment, Cancer, and Radiation Epidemiology Studies I (November 2000 to August 2004) and II (March 2010 to December 2012). Data analysis was conducted from July 2017 to August 2019.

Exposures: Stray radiation dose to the contralateral breast during radiation therapy for the first breast cancer. A novel genetic risk score comprised of genetic variants in the nonhomologous end-joining DNA repair pathway was considered the potential effect modifier, dichotomized as high risk if the score was above the median of 74 and low risk if the score was at or below the median.

Main Outcomes And Measures: The main outcome was risk of contralateral breast cancer associated with stray radiation dose stratified by genetic risk score, age, and latency.

Results: A total of 5953 women were approached for study participation, and 3732 women (62.7%) agreed to participate. The median (range) age at first diagnosis was 46 (23-54) years. After 5 years of latency or more, among women who received the first diagnosis when they were younger than 40 years, exposure to 1.0 Gy (to convert to rad, multiply by 100) or more of stray radiation was associated with a 2-fold increased risk of contralateral breast cancer compared with women who were not exposed (rate ratio, 2.0 [95% CI, 1.1-3.6]). The risk was higher among women with a genetic risk score above the median (rate ratio, 3.0 [95% CI, 1.1-8.1]), and there was no association among women with a genetic risk score below the median (rate ratio, 1.3 [95% CI, 0.5-3.7]). Among younger women with a high genetic risk score, the attributable increased risk for contralateral breast cancer associated with stray radiation dose was 28%.

Conclusions And Relevance: This study found an increased risk of contralateral breast cancer that was attributable to stray radiation exposure among women with a high genetic risk score and who received a first breast cancer diagnosis when they were younger than 40 years after 5 years or more of latency. This genetic risk score may help guide treatment and surveillance for women with breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2019.12259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777239PMC
September 2019

Pre-diagnosis alcohol consumption and mortality risk among black women and white women with invasive breast cancer.

BMC Cancer 2019 Aug 13;19(1):800. Epub 2019 Aug 13.

Department of Population Sciences, Beckman Research Institute, City of Hope, 1500 East Duarte Rd, Duarte, CA, 91010, USA.

Background: Alcohol consumption is associated with increased risk of breast cancer; however, its association with subsequent risk of breast cancer death is unclear.

Methods: We followed 4523 women with complete information on relevant risk factors for mortality; these women were 35 to 64 years of age when diagnosed with incident invasive breast cancer between 1994 and 1998. During follow up (median, 8.6 years), 1055 women died; 824 died from breast cancer. The information on alcohol consumption before diagnosis was collected shortly after breast cancer diagnosis (average: 5.1 months) during an in-person interview which used a structured questionnaire. Multivariable Cox proportional hazards regression models provided hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific mortality, mortality due to causes other than breast cancer, and all-cause mortality associated with alcohol consumption from age 15 years until breast cancer diagnosis and during recent periods of time prior to breast cancer diagnosis.

Results: Average weekly alcohol consumption from age 15 years until breast cancer diagnosis was inversely associated with breast cancer-specific mortality (P = 0.01). Compared to non-drinkers, women in the highest average weekly alcohol consumption category (≥7 drinks/week) had 25% lower risk of breast cancer-specific mortality (HR = 0.75, 95% CI = 0.56-1.00). Breast cancer mortality risk was also reduced among women in the highest average weekly alcohol consumption category in two recent time periods (5-year period ending 2-years prior to breast cancer diagnosis, HR = 0.74, 95% CI = 0.57-0.95; 2-year period immediately prior to breast cancer diagnosis: HR = 0.73, 95% CI = 0.56-0.95). Furthermore, analyses of average weekly alcohol consumption by beverage type from age 15 years until breast cancer diagnosis suggested that wine consumption was inversely associated with breast cancer-specific mortality risk (wine P = 0.06, beer P = 0.24, liquor P = 0.74). No association with any of these alcohol consumption variables was observed for mortality risk due to causes other than breast cancer.

Conclusions: Overall, we found no evidence that alcohol consumption before breast cancer diagnosis increases subsequent risk of death from breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-019-5991-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693233PMC
August 2019

CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy.

Cancer Causes Control 2019 Jan 12;30(1):103-112. Epub 2018 Dec 12.

University of Washington, Seattle, WA, USA.

Purpose: Tamoxifen is widely used to reduce the risk of breast cancer (BC) recurrence and extend disease-free survival among women with estrogen-sensitive breast cancers. Tamoxifen efficacy is thought to be attributable to its active metabolite, which is formed through a reaction catalyzed by the P450 enzyme, CYP2D6. Inhibition of tamoxifen metabolism as a result of germline genetic variation and/or use of CYP2D6-inhibiting medications ("inhibitors") is hypothesized to increase the risk of adverse BC outcomes among women taking tamoxifen.

Methods: The present cohort study of 960 women diagnosed with early-stage BC between 1993 and 1999 examined the association between concomitant use of CYP2D6 inhibitors and adjuvant tamoxifen and the risk of adverse BC outcomes (recurrence, second primary BC, BC mortality), both overall and according to CYP2D6 metabolic phenotype.

Results: Six or more months of CYP2D6 inhibitor use concomitant with tamoxifen was not associated with any appreciable increase in risk of recurrence or second primary BC or BC mortality, and there was no clear evidence of variation by CYP2D6 metabolic phenotype.

Conclusions: These results are consistent with the relatively few other large, population-based studies conducted to date that have not observed an increased risk of adverse BC outcomes associated with CYP2D6 inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-018-1117-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353670PMC
January 2019

Reproductive and menopausal factors and risk of second primary breast cancer after in situ breast carcinoma.

Cancer Causes Control 2019 Jan 11;30(1):113-120. Epub 2018 Dec 11.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M4-C308, Seattle, WA, 98109, USA.

Purpose: In situ breast cancer patients have a higher risk of developing a second primary breast cancer than women in the general population have of developing breast cancer. We have limited understanding of why some women with a previous in situ breast cancer develop second primary breast cancers while others do not.

Methods: In this population-based nested case-control study, we evaluated the association between reproductive and menopausal factors and risk of developing a second primary breast cancer among women with a previous in situ breast cancer. Using conditional logistic regression, these associations were evaluated in 552 cases and 1032 individually matched controls.

Results: Older age at menarche was associated with risk of second primary breast cancer among women with a previous in situ breast cancer (compared to age < 12, age 13: OR 0.60 (0.42, 0.85); age ≥ 14: OR 0.69 (0.47, 1.00); P = 0.07). Breastfeeding for > 12 months was associated with a decreased risk of developing a second primary breast cancer (OR 0.62 (0.39, 0.98)). No associations were observed for other reproductive or menopausal factors evaluated.

Conclusions: Results from this study suggest that reproductive factors may play a role in development of a second primary breast cancer after diagnosis of in situ breast carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-018-1119-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353695PMC
January 2019

CYP2D6 phenotype, tamoxifen, and risk of contralateral breast cancer in the WECARE Study.

Breast Cancer Res 2018 12 10;20(1):149. Epub 2018 Dec 10.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Tamoxifen treatment greatly reduces a woman's risk of developing a second primary breast cancer. There is, however, substantial variability in treatment response, some of which may be attributed to germline genetic variation. CYP2D6 is a key enzyme in the metabolism of tamoxifen to its active metabolites, and variants in this gene have been associated with reduced tamoxifen metabolism. The impact of variation on risk of contralateral breast cancer (CBC) is unknown.

Methods: Germline DNA from 1514 CBC cases and 2203 unilateral breast cancer controls was genotyped for seven single nucleotide polymorphisms, one three-nucleotide insertion-deletion, and a full gene deletion. Each variant has an expected impact on enzyme activity, which in combination allows for the classification of women as extensive, intermediate, and poor metabolizers (EM, IM, and PM respectively). Each woman was assigned one of six possible diplotypes and a corresponding CYP2D6 activity score (AS): EM/EM (AS = 2), EM/IM (AS = 1.5), EM/PM (AS = 1), IM/IM (AS = 0.75), IM/PM (AS = 0.5), and PM/PM (AS = 0). We also collapsed categories of the AS to generate an overall phenotype (EM, AS ≥ 1; IM, AS = 0.5-0.75; PM, AS = 0). Rate ratios (RRs) and 95% confidence intervals (CIs) for the association between tamoxifen treatment and risk of CBC in our study population were estimated using conditional logistic regression, stratified by AS.

Results: Among women with AS ≥ 1 (i.e., EM), tamoxifen treatment was associated with a 20-55% reduced RR of CBC (AS = 2, RR = - 0.81, 95% CI 0.62-1.06; AS = 1.5, RR = 0.45, 95% CI 0.30-0.68; and AS = 1, RR = 0.55, 95% CI 0.40-0.74). Among women with no EM alleles and at least one PM allele (i.e., IM and PM), tamoxifen did not appear to impact the RR of CBC in this population (AS = 0.5, RR = 1.08, 95% CI 0.59-1.96; and AS = 0, RR = 1.17, 95% CI 0.58-2.35) (p for homogeneity = - 0.02).

Conclusion: This study suggests that the CYP2D6 phenotype may contribute to some of the observed variability in the impact of tamoxifen treatment for a first breast cancer on risk of developing CBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-018-1083-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288916PMC
December 2018

Germline Variation and Breast Cancer Incidence: A Gene-Based Association Study and Whole-Genome Prediction of Early-Onset Breast Cancer.

Cancer Epidemiol Biomarkers Prev 2018 09 13;27(9):1057-1064. Epub 2018 Jun 13.

Department of Public Health Sciences, University of Chicago, Chicago, Illinois.

Although germline genetics influences breast cancer incidence, published research only explains approximately half of the expected association. Moreover, the accuracy of prediction models remains low. For women who develop breast cancer early, the genetic architecture is less established. To identify loci associated with early-onset breast cancer, gene-based tests were carried out using exome array data from 3,479 women with breast cancer diagnosed before age 50 and 973 age-matched controls. Replication was undertaken in a population that developed breast cancer at all ages of onset. Three gene regions were associated with breast cancer incidence: ( = 1.23 × 10; replication < 1.00 × 10), ( = 3.57 × 10; replication < 1.00 × 10), and ( = 5.49 × 10; replication < 1.00 × 10). Of the 151 gene regions reported in previous literature, 19 (12.5%) showed evidence of association ( < 0.05) with the risk of early-onset breast cancer in the early-onset population. To predict incidence, whole-genome prediction was implemented on a subset of 3,076 participants who were additionally genotyped on a genome wide array. The whole-genome prediction outperformed a polygenic risk score [AUC, 0.636; 95% confidence interval (CI), 0.614-0.659 compared with 0.601; 95% CI, 0.578-0.623], and when combined with known epidemiologic risk factors, the AUC rose to 0.662 (95% CI, 0.640-0.684). This research supports a role for variation within and in breast cancer incidence, and suggests as a novel risk locus. This analysis supports a shared genetic etiology between women with early- and late-onset breast cancer, and suggests whole-genome data can improve risk assessment. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-17-1185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125194PMC
September 2018

Relationship Between Anthropometric Factors and Risk of Second Breast Cancer Among Women With a History of Ductal Carcinoma In Situ.

JNCI Cancer Spectr 2018 Apr 30;2(2):pky020. Epub 2018 May 30.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.

Background: Women with ductal carcinoma in situ (DCIS) have an elevated risk of a second breast cancer, but few data are available regarding the impact of modifiable lifestyle factors on this risk.

Methods: In a population-based case-control patient study of women with a history of DCIS in western Washington diagnosed between 1996 and 2013, 497 patients diagnosed with DCIS and a second ipsilateral or contralateral invasive or in situ breast cancer were enrolled. There were 965 matched control patients with one DCIS diagnosis. Associations between anthropometric factors and risk of an invasive or in situ second breast cancer event were evaluated using conditional logistic regression. Statistical tests were two-sided.

Results: Obesity (body mass index [BMI] ≥ 30 kg/m) at initial DCIS diagnosis was associated with a 1.6-fold (95% confidence interval [CI] = 1.2 to 2.2) increased risk of any second breast cancer and a 2.2-fold increased risk of a contralateral second breast cancer (95% CI = 1.4 to 3.3) compared with normal weight women (BMI < 25 kg/m). BMI and weight, both at initial DCIS diagnosis and at the time of the second breast cancer diagnosis, were positively associated with risk of any second and second invasive breast cancers (odds ratio = 1.01-1.04, all ≤ .03).

Conclusions: Although additional confirmatory studies are needed, obesity appears to be an important contributor to the risk of second breast cancers within the growing population of women with DCIS. This has potential clinical relevance with respect to identifying which women with a history of DCIS may require more careful monitoring and who may benefit from lifestyle modifications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jncics/pky020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649731PMC
April 2018

Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women's Environmental Cancer and Radiation Epidemiology Study.

J Clin Oncol 2018 05 5;36(15):1513-1520. Epub 2018 Apr 5.

Anne S. Reiner, Julia Sisti, Marinela Capanu, Mark Robson, Xiaolin Liang, Meghan Woods, and Jonine L. Bernstein, Memorial Sloan Kettering Cancer Center; Mark Robson, Cornell University; Roy Shore, New York University School of Medicine, New York, NY; Esther M. John, Cancer Prevention Institute of California, Fremont, and Stanford School of Medicine, Stanford; David V. Conti, Daniel O. Stram, and Duncan C. Thomas, University of Southern California, Los Angeles; Leslie Bernstein, City of Hope National Medical Center, Duarte, CA; Charles F. Lynch, University of Iowa, Iowa City, IA; Jennifer D. Brooks and Julia A. Knight, University of Toronto; Julia A. Knight, Sinai Health System, Toronto, Ontario, Canada; Lene Mellemkjær, Danish Cancer Society Research Center, Copenhagen, Denmark; John D. Boice, Vanderbilt University Medical Center and the Vanderbilt-Ingram Cancer Center, Nashville, TN; Patrick Concannon, University of Florida, Gainesville, FL; Marc Tischkowitz, University of Cambridge, Cambridge, United Kingdom; David Duggan, Translational Genomics Research Institute, Phoenix, AZ; and Kathleen E. Malone, Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose The Women's Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2 mutations. With the completion of WECARE II, updated risk estimates are reported. Additional analyses that exclude women negative for deleterious mutations in ATM, CHEK2*1100delC, and PALB2 were performed. Patients and Methods The WECARE Study is a population-based case-control study that compared 1,521 CBC cases with 2,212 individually matched unilateral breast cancer (UBC) controls. Participants were younger than age 55 years when diagnosed with a first invasive breast cancer between 1985 and 2008. Women were interviewed about breast cancer risk factors, including family history. A subset of women was screened for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2. Rate ratios (RRs) were estimated using multivariable conditional logistic regression. Cumulative absolute risks (ARs) were estimated by combining RRs from the WECARE Study and population-based SEER*Stat cancer incidence data. Results Women with any first-degree relative with breast cancer had a 10-year AR of 8.1% for CBC (95% CI, 6.7% to 9.8%). Risks also were increased if the relative was diagnosed at an age younger than 40 years (10-year AR, 13.5%; 95% CI, 8.8% to 20.8%) or with CBC (10-year AR, 14.1%; 95% CI, 9.5% to 20.7%). These risks are comparable with those seen in BRCA1/2 deleterious mutation carriers (10-year AR, 18.4%; 95% CI, 16.0% to 21.3%). In the subset of women who tested negative for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2, estimates were unchanged. Adjustment for known breast cancer single-nucleotide polymorphisms did not affect estimates. Conclusion Breast cancer family history confers a high CBC risk, even after excluding women with deleterious mutations. Clinicians are urged to use detailed family histories to guide treatment and future screening decisions for young women with breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2017.77.3424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959199PMC
May 2018

The association of mammographic density with risk of contralateral breast cancer and change in density with treatment in the WECARE study.

Breast Cancer Res 2018 03 22;20(1):23. Epub 2018 Mar 22.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Mammographic density (MD) is an established predictor of risk of a first breast cancer, but the relationship of MD to contralateral breast cancer (CBC) risk is not clear, including the roles of age, mammogram timing, and change with treatment. Multivariable prediction models for CBC risk are needed and MD could contribute to these.

Methods: We conducted a case-control study of MD and CBC risk in phase II of the WECARE study where cases had a CBC diagnosed ≥ 2 years after first diagnosis at age <55 years and controls had unilateral breast cancer (UBC) with similar follow-up time. We retrieved film mammograms of the unaffected breast from two time points, prior to/at the time of the first diagnosis (253 CBC cases, 269 UBC controls) and ≥ 6 months up to 48 months following the first diagnosis (333 CBC cases, 377 UBC controls). Mammograms were digitized and percent MD (%MD) was measured using the thresholding program Cumulus. Odds ratios (OR) and 95% confidence intervals (CI) for association between %MD and CBC, adjusted for age, treatment, and other factors related to CBC, were estimated using logistic regression. Linear regression was used to estimate the association between treatment modality and change in %MD in 467 women with mammograms at both time points.

Results: For %MD assessed following diagnosis, there was a statistically significant trend of increasing CBC with increasing %MD (p = 0.03). Lower density (<25%) was associated with reduced risk of CBC compared to 25 to < 50% density (OR 0.69, 95% CI 0.49, 0.98). Similar, but weaker, associations were noted for %MD measurements prior to/at diagnosis. The relationship appeared strongest in women aged < 45 years and non-existent in women aged 50 to 54 years. A decrease of ≥ 10% in %MD between first and second mammogram was associated marginally with reduced risk of CBC (OR 0.63, 95% CI 0.40, 1.01) compared to change of <10%. Both tamoxifen and chemotherapy were associated with statistically significant 3% decreases in %MD (p < 0.01).

Conclusions: Post-diagnosis measures of %MD may be useful to include in CBC risk prediction models with consideration of age at diagnosis. Chemotherapy is associated with reductions in %MD, similar to tamoxifen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-018-0948-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863854PMC
March 2018

Body mass index at age 18 years and recent body mass index in relation to risk of breast cancer overall and ER/PR/HER2-defined subtypes in white women and African-American women: a pooled analysis.

Breast Cancer Res 2018 01 22;20(1). Epub 2018 Jan 22.

Department of Population Sciences, Beckman Research Institute, City of Hope, 1500 East Duarte Rd., Duarte, CA, 91010, USA.

Background: Although it has been well-documented that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer, it is unclear whether these associations differ among breast cancer subtypes defined by the tumor protein expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).

Methods: We evaluated the associations of body mass index (BMI) at age 18 years and recent BMI in relation to risk of breast cancer overall and ER/PR/HER2-defined subtypes, in 6320 women (3934 case-patient participants, 2386 control participants) aged 35-64 years, who participated in one of three population-based case-control studies. We estimated multivariable-adjusted odd ratios (ORs) and corresponding 95% confidence intervals (CIs) using polychotomous unconditional logistic regression methods for case-control comparisons in premenopausal women and postmenopausal women.

Results: BMI at age 18 years was inversely associated with risk of breast cancer, particularly among premenopausal women (≥ 25 vs. < 20 kg/m, OR = 0.72, 95% CI = 0.53-0.96; per 5 kg/m increase, OR = 0.83, 95% CI = 0.73-0.95). This inverse association did not differ across ER/PR/HER2-defined subtypes or by race (white women, African-American women). Recent BMI was not associated with risk of premenopausal breast cancer after adjustment for BMI at age 18 years; nevertheless, the analysis for the joint effects of BMI at age 18 years and recent BMI showed that premenopausal women in the highest categories of the two BMI measures (≥ 25 kg/m at age 18 years and ≥ 30 kg/m for recent BMI) had 46% lower risk of breast cancer than premenopausal women in the lowest categories of the two BMI measures (< 20 kg/m at age 18 years and < 25 kg/m for recent BMI; OR = 0.54, 95% CI = 0.38-0.78). Neither measure of BMI was statistically significantly associated with risk of postmenopausal breast cancer.

Conclusion: Our findings indicate that high BMI near the end of adolescence decreases risk of all ER/PR/HER2-defined subtypes of premenopausal breast cancer and also suggest that this benefit could be maximized among premenopausal women who consistently have high BMI during their premenopausal years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-017-0931-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778748PMC
January 2018

Family History and Risk of Second Primary Breast Cancer after Breast Carcinoma.

Cancer Epidemiol Biomarkers Prev 2018 03 16;27(3):315-320. Epub 2018 Jan 16.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Incidence rates of breast carcinomas have increased due to widespread adoption of mammography. Very little is known about why some women with breast cancer later develop second primary breast cancers. In this population-based nested case-control study among breast cancer survivors, including 539 cases with a second primary breast cancer and 994 matched controls, we evaluated the association between first-degree family history of breast cancer and risk of developing a second primary breast cancer. First-degree family history of breast cancer was associated with an increased risk of developing a second primary breast cancer among women with a previous breast cancer [odds ratio (OR) = 1.33, 95% confidence interval (CI), 1.05-1.69] and those with two or more affected first-degree relatives had an even higher risk (OR = 1.94; 95% CI, 1.15-3.28). Those whose relative was diagnosed at less than 50 years old were more likely to develop a second primary breast cancer (OR = 1.78; 95% CI, 1.24-2.57). No difference in risks associated with number or age of affected relatives was observed by menopausal status. Results from this study suggest that first-degree family history of breast cancer may be an important risk factor for development of a second primary breast cancer among women with a previous breast cancer. Given the growing population of breast cancer survivors, a better understanding of risk factors associated with development of a second primary breast cancer is needed to further understand risk. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-17-0837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835196PMC
March 2018

Bisphosphonate Use and Risk of Recurrence, Second Primary Breast Cancer, and Breast Cancer Mortality in a Population-Based Cohort of Breast Cancer Patients.

Cancer Epidemiol Biomarkers Prev 2018 02 18;27(2):165-173. Epub 2017 Dec 18.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Studies of bisphosphonate use and breast cancer recurrence have produced conflicting results. Analyses of large adjuvant trials suggest that bisphosphonates reduce recurrence risk only in postmenopausal women. We assessed the effect of noncancer treatment-related bisphosphonate use on breast cancer outcomes in a population-based prognostic cohort of women with early-stage invasive breast cancer ( = 1,813; median follow-up = 11.8 years). Using medical record, interview, and cancer registry data, information was assembled on risk factors, cancer treatment, medication use, and outcomes. Statistical analyses used Cox proportional hazards regression models. Bisphosphonate use was associated with a significantly decreased risk of a breast cancer event [locoregional/distant recurrence or second primary breast cancer; HR ever use, 0.65; 95% confidence interval (CI), 0.47-0.90]. Reduced risks were observed in both pre/peri and postmenopausal women, in both ER-negative and ER-positive breast cancers, and for both earlier and later recurrences. Bisphosphonate use was also associated with a significantly decreased risk of breast cancer mortality (HR, 0.40; 95% CI, 0.23-0.69). Bisphosphonate use was associated with a reduction in risk of breast cancer events and improved breast cancer-specific survival in women with early-stage breast cancer. We hypothesize that the benefit of bisphosphonates on breast cancer outcomes may be present primarily in women with low bone density and regardless of menopausal status. Our findings suggest further consideration of bone density status as a modifier of bisphosphonate's potential beneficial benefits on breast cancer outcomes is warranted. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-17-0556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021196PMC
February 2018

Association analysis identifies 65 new breast cancer risk loci.

Nature 2017 11 23;551(7678):92-94. Epub 2017 Oct 23.

Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature24284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798588PMC
November 2017

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.

Nat Genet 2017 Dec 23;49(12):1767-1778. Epub 2017 Oct 23.

Department of Epidemiology, University of California, Irvine, Irvine, California, USA.

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.3785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808456PMC
December 2017

Agreement between self-reported and register-based cardiovascular events among Danish breast cancer survivors.

J Cancer Surviv 2018 02 29;12(1):95-100. Epub 2017 Sep 29.

Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.

Purpose: We examined the degree of over- and under-reporting of cardiovascular diseases (CVDs) among female breast cancer survivors comparing self-reports to diagnostic codes from the Danish National Patient Register (NPR).

Methods: The study comprised 357 Danish breast cancer patients from the WECARE study who completed a telephone interview concerning CVDs. Disease diagnoses for these women were obtained from the NPR. Agreement was calculated as the number of diagnoses that were both self-reported and in the NPR divided by (1) number of self-reported diagnoses (over-reporting) or (2) number of diagnoses in the NPR (under-reporting).

Results: In total, 68 women reported 96 specific cardiovascular outcomes of which 56 (58%) were found in the NPR. Ninety cardiovascular diagnoses were found in the NPR of which 56 (62%) were specifically reported at the interview. There was 80% agreement as to the occurrence of a cardiovascular diagnosis overall. Of 289 women reporting no CVD, 273 (94%) had no diagnoses in the NPR.

Conclusions: Breast cancer survivors seem to report absence of CVD accurately, but they both over-report and under-report specific cardiovascular diagnoses. Using a broader definition of CVDs improves the agreement between self-reported and NPR data.

Implications For Cancer Survivors: Determining how cancer treatments affect the risk of cardiovascular morbidities is essential, and the development of high-quality methods for collecting such data is critical. While self-reported data are adequate for assessing the presence of any CVD condition, medical record review will yield higher quality data on specific CVD conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11764-017-0648-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790612PMC
February 2018

Hormone receptor status of a first primary breast cancer predicts contralateral breast cancer risk in the WECARE study population.

Breast Cancer Res 2017 Jul 19;19(1):83. Epub 2017 Jul 19.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history.

Methods: The Women's Environmental Cancer and Radiation Epidemiology Study is a population-based case-control study of 1521 CBC cases and 2212 individually-matched controls with unilateral breast cancer. Detailed information about breast cancer risk factors, treatment for and characteristics of first tumors, including estrogen receptor (ER) and progesterone receptor (PR) status, was obtained by telephone interview and medical record abstraction. Multivariable risk ratios (RRs) and 95% confidence intervals (CIs) were estimated in conditional logistic regression models, adjusting for demographics, treatment, and personal medical and family history. A subset of women was screened for BRCA1/2 mutations.

Results: Lobular histology of the first tumor was associated with a 30% increase in CBC risk (95% CI 1.0-1.6). Compared to women with ER+/PR+ first tumors, those with ER-/PR- tumors had increased risk of CBC (RR = 1.4, 95% CI 1.1-1.7). Notably, women with ER-/PR- first tumors were more likely to develop CBC with the ER-/PR- phenotype (RR = 5.4, 95% CI 3.0-9.5), and risk remained elevated in multiple subgroups: BRCA1/2 mutation non-carriers, women younger than 45 years of age, women without a breast cancer family history, and women who were not treated with tamoxifen.

Conclusions: Having a hormone receptor negative first primary breast cancer is associated with increased risk of CBC. Women with ER-/PR- primary tumors were more likely to develop ER-/PR- CBC, even after excluding BRCA1/2 mutation carriers. Hormone receptor status, which is routinely evaluated in breast tumors, may be used clinically to determine treatment protocols and identify patients who may benefit from increased surveillance for CBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-017-0874-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5517810PMC
July 2017

Alcohol Intake and Risk of Breast Cancer by Histologic Subtype and Estrogen Receptor Status Among Women Aged 55 to 74 Years.

Horm Cancer 2017 08 31;8(4):211-218. Epub 2017 May 31.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M4-C308, Seattle, WA, 98109, USA.

Previous studies suggest that alcohol consumption and risk of breast cancer may differ by histologic subtype and hormone receptor status, though results are not entirely consistent. In this population-based case-control study, we evaluated the association between alcohol consumption and risk of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and invasive ductal-lobular carcinoma (IDLC) overall and by estrogen receptor (ER) status, among women aged 55-74 years of age. Using polytomous regression, associations between current alcohol consumption, overall and by type of alcohol, and breast cancer risk were evaluated in 891 controls and 905 IDC, 567 ILC, and 489 IDLC cases. Current alcohol use was moderately associated with risk of ILC (odds ratio = 1.25, 95% confidence interval 0.99, 1.58) with a positive dose-response relationship based on average number of drinks per week consumed (P  = 0.0005). When further stratified by ER status, alcohol use was positively associated with risk of ER+ ILC (P = 0.002) and ER+ IDC (P = 0.02), but inversely associated with risk of ER-IDC (P = 0.01). No association between alcohol and risk of IDLC tumors was observed. While the link between alcohol consumption and breast cancer risk is well established, our results suggest that the increased risk associated with alcohol is largely limited to ER+ ILC and ER+ IDC. Thus, avoiding or moderating alcohol consumption may be one way that women can lower their risks of these forms of breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12672-017-0297-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779634PMC
August 2017

Alcohol consumption and cigarette smoking in combination: A predictor of contralateral breast cancer risk in the WECARE study.

Int J Cancer 2017 09 31;141(5):916-924. Epub 2017 May 31.

Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.

Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a large population-based case-control study of women with breast cancer where cases (N = 1,521) had asynchronous CBC and controls (N = 2,212), matched on survival time and other factors, had unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease characteristics and other factors. There was some evidence for an association between CBC risk and current drinking or current smoking at the time of first breast cancer diagnosis, but the increased risk occurred primarily among women exposed to both (RR = 1.62, 95% CI 1.24-2.11). CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR = 1.54, 95% CI 1.18-1.99). In the subset of women with detailed information on amount consumed, smoking an average of ≥10 cigarettes per day following diagnosis was also associated with increased CBC risk (RR = 1.50, 95% CI 1.08-2.08; p-trend = 0.03). Among women with a diagnosis of breast cancer, information on current drinking and smoking could contribute to the prediction of CBC risk. Women who both drink and smoke may represent a group who merit targeted lifestyle intervention to modify their risk of CBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.30791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518236PMC
September 2017

Association of Common Genetic Variants With Contralateral Breast Cancer Risk in the WECARE Study.

J Natl Cancer Inst 2017 10;109(10)

Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York,NY, USA.

Background: Women with unilateral breast cancer (UBC) are at risk of developing a subsequent contralateral breast cancer (CBC). Common variants are associated with breast cancer risk. Whether these influence CBC risk is unknown.

Methods: Participants were breast cancer cases from the population-based Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study. Sixty-seven established breast cancer risk loci were genotyped directly or by imputation in 1459 case subjects with CBC and 2126 UBC control subjects. An unweighted polygenic risk score (PRS) was created by summing the number of risk alleles for each directly genotyped single nucleotide polymorphism (SNP), or for imputed loci, the imputed dosage. A weighted PRS was calculated similarly, but where each SNP's contribution was weighted by the published per-allele log odds ratio. Unweighted and weighted polygenic risk scores and CBC risk were modeled using conditional logistic regression. Cumulative CBC risk was estimated and benchmarked using Surveillance, Epidemiology, and End Results population incidence rates.

Results: Both unweighted and weighted PRS were statistically significantly associated with CBC risk. The adjusted risk ratio of CBC in women in the upper quartile of unweighted PRS compared with the lowest quartile was 1.63 (95% confidence interval [CI] = 1.33 to 2.00). The estimated 10-year cumulative risk for women in the upper quartile of the unweighted PRS was 7.4% (95% CI = 6.0% to 9.1%). For women in the upper quartile of the weighted PRS, the risk ratio for CBC was 1.75 (95% CI = 1.41 to 2.18) compared with women in the lowest quartile. There was no statistically significant heterogeneity by age, treatment (radiation therapy dose, tamoxifen, chemotherapy), estrogen receptor status of the first primary, histology of the first primary, length of at-risk period for CBC, or breast cancer family history.

Conclusions: Common genomic variants associated with the development of first primary breast cancer are also associated with the development of CBC; the risk is strongest among those who carry more risk alleles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djx051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939625PMC
October 2017

Reproductive factors and the risk of triple-negative breast cancer in white women and African-American women: a pooled analysis.

Breast Cancer Res 2017 01 13;19(1). Epub 2017 Jan 13.

Department of Population Sciences, Beckman Research Institute, 1500 East Duarte Rd. Duarte, City of Hope, CA, 91010, USA.

Background: Early age at menarche, nulliparity, late age at first completed pregnancy, and never having breastfed, are established breast cancer risk factors. However, among breast cancer subtypes, it remains unclear whether all of these are risk factors for triple-negative breast cancer (TNBC).

Methods: We evaluated the associations of these reproductive factors with TNBC, in 2658 patients with breast cancer (including 554 with TNBC) and 2448 controls aged 20-64 years, who participated in one of the three population-based case-control studies: the Women's Contraceptive and Reproductive Experiences Study, the Women's Breast Carcinoma in situ Study, or the Women's Learning the Influence of Family and Environment Study. We used multivariable polychotomous unconditional logistic regression methods to conduct case-control comparisons among breast cancer subtypes defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression status.

Results: TNBC risk decreased with increasing duration of breastfeeding (P  = 0.006), but age at menarche, age at first completed pregnancy, and nulliparity were not associated with risk of TNBC. Parous women who breastfed for at least one year had a 31% lower risk of TNBC than parous women who had never breastfed (odds ratio, OR = 0.69; 95% confidence interval, CI = 0.50-0.96). The association between breastfeeding and risk of TNBC was modified by age and race. Parous African-American women aged 20-44 years who breastfed for 6 months or longer had an 82% lower risk of TNBC than their counterparts who had never breastfed (OR = 0.18, 95% CI = 0.07-0.46).

Conclusions: Our data indicate that breastfeeding decreases the risk of TNBC, especially for younger African-American women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-016-0799-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237290PMC
January 2017

Body mass index, weight change, and risk of second primary breast cancer in the WECARE study: influence of estrogen receptor status of the first breast cancer.

Cancer Med 2016 11 3;5(11):3282-3291. Epub 2016 Oct 3.

Memorial Sloan Kettering Cancer Center, New York, New York.

Studies examining the relationship between body mass index (BMI) and risk of contralateral breast cancer (CBC) have reported mixed findings. We previously showed that obese postmenopausal women with estrogen receptor (ER)-negative breast cancer have a fivefold higher risk of CBC compared with normal weight women. In the current analysis, we reexamined this relationship in the expanded Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study, focusing on the impact of menopausal status and ER status of the first breast cancer. The WECARE Study is a population-based case-control study of young women with CBC (cases, N = 1386) and with unilateral breast cancer (controls, N = 2045). Rate ratios (RR) and 95% confidence intervals (CI) were calculated to assess the relationship between BMI and risk of CBC stratified by menopausal and ER status. Positive associations with obesity and weight gain were limited to women who became postmenopausal following their first primary breast cancer. Among those with an ER-negative first breast cancer, obesity (vs. normal weight) at first diagnosis was associated with an increased risk of CBC (RR = 1.9, 95% CI: 1.02, 3.4). Also, weight gain of ≥10 kg after first diagnosis was associated with an almost twofold increased risk of CBC (RR = 1.9, 95% CI: 0.99, 3.8). These results suggest that women with an ER-negative first primary cancer who are obese at first primary diagnosis or who experience a large weight gain afterward may benefit from heightened surveillance. Future studies are needed to address the impact of weight loss interventions on risk of CBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119984PMC
November 2016

Systemic therapy for breast cancer and risk of subsequent contralateral breast cancer in the WECARE Study.

Breast Cancer Res 2016 07 12;18(1):65. Epub 2016 Jul 12.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Treatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment characteristics.

Methods: The population-based WECARE Study included 1521 cases with CBC and 2212 age- and year of first diagnosis-matched controls with unilateral breast cancer recruited during two phases in the USA, Canada, and Denmark. Women were diagnosed with a first breast cancer before age 55 years during 1985-2008. Abstraction of medical records provided detailed treatment information, while information on risk factors was obtained during telephone interviews. Risk ratios (RRs) and 95 % confidence intervals (CIs) for CBC were obtained from multivariable conditional logistic regression models.

Results: Compared with never users of tamoxifen, the RR of CBC was lower for current users of tamoxifen (RR = 0.73; 95 % CI = 0.55-0.97) and for past users within 3 years of last use (RR = 0.73; 95 % CI = 0.53-1.00). There was no evidence of an increased risk of estrogen receptor-negative CBC associated with ever use of tamoxifen or use for 4.5 or more years. Use of chemotherapy (ever versus never use) was associated with a significantly reduced RR of developing CBC 1-4 years (RR = 0.59; 95 % CI = 0.45-0.77) and 5-9 years (RR = 0.73; 95 % CI = 0.56-0.95) after first breast cancer diagnosis. RRs of CBC associated with tamoxifen or with chemotherapy use were independent of age, family history of breast cancer, body mass index and tumor characteristics of the first breast cancer with the exception that the RR of CBC was lower for lobular histology compared with other histologies.

Conclusion: Our findings are consistent with previous studies showing that treatment with tamoxifen or chemotherapy is associated with a lower risk of CBC although the risk reduction appears to last for a limited time period after treatment is completed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-016-0726-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940926PMC
July 2016
-->